The sterilization of liquid media is an essential precondition when employing production methods in the field of biotechnology and food technology. The objective is reliable and complete depletion of microorganisms and/or viruses hand in hand with virtually complete preservation of valuable substances. Sterilization is applied both to the feed stock (e.g. nutrient media for fermentations) and end products (e.g. milk products or pharmaceutical active proteins). For the food industry, the sterilization techniques are used, inter alia, with a view to longer shelf life, whereas their use in the pharmaceutical industry is regulated by strict quality assurance requirements. For example, the use of pharmaceutical products of human or animal origin requires a number of virus deactivation steps which are based on different principles of action and must each ensure viral depletion by at least four powers of ten. The need to ensure “viral safety” of course also applies to pharmaceuticals produced by genetic engineering methods.
One of the viral depletion methods proposed in the literature as having minimal impact on the product is the irradiation with ultraviolet light. The treatment of plasma and blood products with UV light is known in principle. As early as during the second world war, large quantities of plasma were collected and irradiated with UV light. The UV treatment of blood derivatives is of particular interest, however, with respect to non-enveloped, heat-resistant viruses. Chin et al (Chin, S., Jin, R., Wang, X. L., Hamman, J., Gerard Marx, Xlaode Mou, Inger Andersson, Lars-Olof Lindquist, and Bernhard Horowitz (1997). Virucidal Treatment of Blood Protein Products with UVC Radiation. Photochemistry and Photobiology 65(3): 432-435) were able to show that a treatment of plasma products with UV light results in deactivation of hepatitis A and parvoviruses.
UV irradiation is aimed at mutagenic changes in the genetic material of the microorganisms or viruses which, above a minimum radiation dose, lose their ability to reproduce. It is an object of the invention to develop for this purpose a reliable and optimally effective apparatus for irradiation with UV light.
Problems in the use of reactors for radiating ultraviolet light into liquid reaction media are caused by the fact that the radiation intensity in the medium to be treated decreases exponentially with increasing distance from the radiation source. Microorganisms and viruses at a greater distance from the radiation source are therefore destroyed more slowly or even not at all. Because of this effect, which is magnified considerably as the optical absorptance of the medium increases, very large irradiation surface areas are employed in the prior art, as found e.g. in thin-film reactors. The thin-film reactors currently in use can be scaled up only with difficulty to industrial scales, as the only way to keep the film thickness constant in the scale-up is to increase the diameter in proportion with the throughput, which on an industrial scale results in infeasibly large reactors. A further negative factor is the unfavourable residence time behaviour of the liquid films, which given the generally low penetration depth of the UV radiation to the reaction medium are necessarily very thin and consequently exhibit laminar flow, in which any transfer transverse to the principal flow direction is absent by definition. The layers close to the wall remain for considerably longer times, because of the velocity profile dropping linearly to zero towards the wall, than the layers further away from the wall. In order to achieve the minimum radiation dose necessary for destruction even in the more rapidly flowing liquid layer far from the wall, the mean residence time of the film has to be increased. This, however, leads to an increased radiation exposure and consequently to greater damage to the products.
Also known and described are so-called annular-gap reactors. A UV annular-gap reactor of conventional design consists of a tubular metal housing set into which is a quartz tube containing a rod-shaped UV radiation source, thereby forming an annular-gap chamber. In this reactor type, the reaction medium flows through the annular chamber only in an axial direction, which likewise is not advantageous with a view to good mass transfer—a similar situation as with the thin-film reactors.
The disadvantages described of the reactor types should be capable of being overcome by more favourable flow routing which, in addition to a narrow residence time spectrum, also permit good transfer in the liquid perpendicular to the principal flow direction. Proposals for this purpose include tangential-inflow annular gap reactors From EP 803 472 A1 e.g. is a reactor for radiating ultraviolet light into a reaction medium, comprising an annular chamber as the irradiation zone, in which the design of the inlet is such that the reaction medium enters the annular chamber tangentially.
The performance of a reactor with tangential inflow has marginal advantages, compared with a “classic” annular-gap reactor. Process engineering studies show that wall friction causes the tangential flow profile to be transformed into an axial profile very soon after the inlet. The Dean vortices, which are theoretically postulated at least for the region of tangential cross flow and by means of which the cross-transfer of the reaction medium within the annular gap is to be intensified, are not present according to visual studies and CFD studies (flow simulation), which means that tangential-inflow annular-gap reactors of this type do permit some improvement in the mixing behaviour, but still do not allow complete exchange. The secondary flow and the concomitant improved mass transfer is therefore restricted to the zones near the inlet.
It was possible to demonstrate that this behaviour can be tolerated in the treatment of weakly absorbing reaction media (e.g. water treatment), as mixing is adequate for this purpose and the UV dose can be increased to circumvent this drawback. For applications in connection with the treatment of protein solutions this appeared impossible, as the proteins would suffer irreversible damage in the process.
It is therefore novel and surprizing that the reactors of the type mentioned at the outset are also suitable for treating virus-contaminated protein solutions if the radiation chamber over its entire length includes means for additional radial flow routing of the reaction medium and in particular if, relative to the diameter of the housing, a specific reactor length is not exceeded. The proposed L/D ratios should preferably be less than 100.
As made clear by the above description, it is an object of the invention to provide apparatuses of the type mentioned at the outset having an optimized, more uniform mixing behaviour for the reaction medium.